Successful treatment of cancer by neutrons, photons, mixed neutrons and photons, or radiation combined with chemotherapy necessitates a knowledge of the normal tissue sequelae associated with the cure of the tumor. This is expressed as the dose of photon irradiation which results in specific late effects (especially carcinogenesis) to the dose of neutron irradiation (or other test treatment) which results in the same specific effects (RBE values). The aim of this investigation is to obtain these values for sequelae in the brain, spinal cord, and lung and from neutrons alone or photons alone to investigate mechanisms of action of the two modalities in normal tissues. Currently, fast neutrons are being used in the United Staees, Europe and Japan in the treatment of cancer patients. New hospital-based facilities are under construction in the United States. Normal tissue tolerances have been approached, especially in the brain and spinal cord in the patient population which has been treated. As early as 1978 our data, from large animals using a clinical fractionated schedule and total doses of neutrons or photons encompassing the clinical range, have yielded RBE values of greater than 4 in the therapeutic dose range. These values have been shown to reflect the unacceptable late sequelae in the patient population. This ongoing study will continue to evaluate sequelae utilizing functional and quantitative methods. It is especially important to obtain RBE values for onset, incidence and degree of malignancy with neutron therapy alone. These data can be used as a comparison to test other treatment schedules (mixed beam with or without chemotherapy) in large animals using CT, radionuclide evaluation, or quantitative histopathology or biochemistry.